The specific aims of this proposal are to examine the effects of adrenergic stimuli (alpha-adrenergic agonists, beta-adrenergic agonists, and sympathetic neural stimulation) on specific levels of airway function in the tracheas of living dogs. At the level of tracheal smooth muscle, we will test the possible alpha-adrenergic enhancing properties of histamine, serotonin, cool temperatures, ozone, and sulfur dioxide. At the level of tracheal parasympathetic efferent nerves, we will examine the effects of adrenergic stimuli on cholinergic neurotransmission. At the level of tracheal mast cells, we will test the possible inhibition of the severity of mast cell reactions by electrical stimulation of sympathetic nerves. For these studies, dogs will be anesthetized and their lungs will be mechanically ventilated via low cervical tracheostomies. Pharmacologic agents will be injected selectively into the tracheal circulation of each dog. Smooth muscle tension will be measured isometrically in discrete segments of the tracheal posterior membrane in situ. Specific autonomic nerves will be cut and stimulated electrically. The severity of mast cell reactions, induced by tracheal injections of compound 48/80, will be measured physiologically (by monitoring tracheal tension) and biochemiclly (by measuring tracheal arteriovenous differences in plasma concentrations of histamine). The findings of these studies should provide insight as to the causes and consequences of the abnormalities in adrenergic regulation (e.g., alpha-adrenergic hyperresponsiveness) observed in patients with asthma.